To reduce the development of drug-resistant bacteria and maintain the effectiveness of ofloxacin tablets and other antibacterial drugs, ofloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Ofloxacin tablets are a synthetic broad-spectrum antimicrobial agent for oral administration. Chemically, ofloxacin,USP, a fluorinated carboxyquinolone, is the racemate, (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7 H-pyrido[1,2,3- de]-1,4-benzoxazine-6-carboxylic acid. The chemical structure is:

C 18H 20FN 3O 4

MW= 361.4

Ofloxacin, USP is an off-white to pale yellow crystalline powder. The molecule exists as a zwitterion at the pH conditions in the small intestine. The relative solubility characteristics of ofloxacin, USP at room temperature, as defined by USP nomenclature, indicate that ofloxacin, USP is considered to be soluble in aqueous solutions with pH between 2 and 5. It is sparingly to slightly soluble in aqueous solutions with pH 7 (solubility falls to 4 mg/mL) and freely soluble in aqueous solutions with pH above 9. Ofloxacin, USP has the potential to form stable coordination compounds with many metal ions. This in vitro chelation potential has the following formation order: Fe +3 > Al +3 > Cu +2 > Ni +2 > Pb +2 > Zn +2 > Mg +2 > Ca +2 > Ba +2.

Ofloxacin tablets contain the following inactive ingredients: anhydrous lactose, modified corn starch, hydroxypropyl cellulose, hypromellose, magnesium stearate, polyethylene glycol, polysorbate 80, sodium starch glycolate, and titanium dioxide.

Following oral administration, the bioavailability of ofloxacin in the tablet formulation is approximately 98%. Maximum serum concentrations are achieved one to two hours after an oral dose. Absorption of ofloxacin after single or multiple doses of 200 to 400 mg is predictable, and the amount of drug absorbed increases proportionately with the dose. Ofloxacin has biphasic elimination. Following multiple oral doses at steady-state administration, the half-lives are approximately 4 to 5 hours and 20 to 25 hours. However, the longer half-life represents less than 5% of the total AUC. Accumulation at steady-state can be estimated using a half-life of 9 hours. The total clearance and volume of distribution are approximately similar after single or multiple doses. Elimination is mainly by renal excretion. The following are mean peak serum concentrations in healthy 70 to 80 kg male volunteers after single oral doses of 200, 300, or 400 mg of ofloxacin or after multiple oral doses of 400 mg.

Steady-state concentrations were attained after four oral doses, and the area under the curve (AUC) was approximately 40% higher than the AUC after single doses. Therefore, after multiple-dose administration of 200 mg and 300 mg doses, peak serum levels of 2.2 mcg/mL and 3.6 mcg/mL, respectively, are predicted at steady-state.

In vitro, approximately 32% of the drug in plasma is protein bound.

The single dose and steady-state plasma profiles of ofloxacin injection were comparable in extent of exposure (AUC) to those of ofloxacin tablets when the injectable and tablet formulations of ofloxacin were administered in equal doses (mg/mg) to the same group of subjects. The mean steady-state AUC (0 to 12) attained after the intravenous administration of 400 mg over 60 min was 43.5 mcg•h/mL; the mean steady-state AUC (0 to 12) attained after the oral administration of 400 mg was 41.2 mcg•h/mL (two one-sided t-test, 90% confidence interval was 103 to 109) (see following chart).

Between 0 and 6 h following the administration of a single 200 mg oral dose of ofloxacin to 12 healthy volunteers, the average urine ofloxacin concentration was approximately 220 mcg/mL. Between 12 and 24 hours after administration, the average urine ofloxacin level was approximately 34 mcg/mL.

Following oral administration of recommended therapeutic doses, ofloxacin has been detected in blister fluid, cervix, lung tissue, ovary, prostatic fluid, prostatic tissue, skin, and sputum. The mean concentration of ofloxacin in each of these various body fluids and tissues after one or more doses was 0.8 to 1.5 times the concurrent plasma level. Inadequate data are presently available on the distribution or levels of ofloxacin in the cerebrospinal fluid or brain tissue.

Ofloxacin has a pyridobenzoxazine ring that appears to decrease the extent of parent compound metabolism. Between 65% and 80% of an administered oral dose of ofloxacin is excreted unchanged via the kidneys within 48 hours of dosing. Studies indicate that less than 5% of an administered dose is recovered in the urine as the desmethyl or N-oxide metabolites. Four to eight percent of an ofloxacin dose is excreted in the feces. This indicates a small degree of biliary excretion of ofloxacin.

The administration of ofloxacin tablets with food does not affect the C max and AUC ∞ of the drug, but T max is prolonged.

Clearance of ofloxacin is reduced in patients with impaired renal function (creatinine clearance rate ≤ 50 mL/min), and dosage adjustment is necessary (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).

Following oral administration to healthy elderly subjects (65 to 81 years of age), maximum plasma concentrations are usually achieved one to two hours after single and multiple twice-daily doses, indicating that the rate of oral absorption is unaffected by age or gender. Mean peak plasma concentrations in elderly subjects were 9 to 21% higher than those observed in younger subjects. Gender differences in the pharmacokinetic properties of elderly subjects have been observed. Peak plasma concentrations were 114% and 54% higher in elderly females compared to elderly males following single and multiple twice-daily doses. [This interpretation was based on study results collected from two separate studies.] Plasma concentrations increase dose-dependently with the increase in doses after single oral dose and at steady-state. No differences were observed in the volume of distribution values between elderly and younger subjects. As in younger subjects, elimination is mainly by renal excretion as unchanged drug in elderly subjects, although less drug is recovered from renal excretion in elderly subjects. Consistent with younger subjects, less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites in the elderly. A longer plasma half-life of approximately 6.4 to 7.4 hours was observed in elderly subjects, compared with 4 to 5 hours for young subjects. Slower elimination of ofloxacin is observed in elderly subjects as compared with younger subjects which may be attributable to the reduced renal function and renal clearance observed in the elderly subjects. Because ofloxacin is known to be substantially excreted by the kidney, and elderly patients are more likely to have decreased renal function, dosage adjustment is necessary for elderly patients with impaired renal function as recommended for all patients (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).

Ofloxacin is a quinolone antimicrobial agent. The mechanism of action of ofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.

Ofloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive microorganisms. Ofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.

Fluoroquinolones, including ofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides and β-lactam antibiotics, including penicillins. Fluoroquinolones may, therefore, be active against bacteria resistant to these antimicrobials.

Resistance to ofloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10 -9 to 10 -11). Although cross-resistance has been observed between ofloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to ofloxacin.

Ofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Aerobic Gram-Positive Microorganisms

Staphylococcus aureus (methicillin-susceptible strains)

Streptococcus pneumoniae (penicillin-susceptible strains)

Streptococcus pyogenes

Aerobic Gram-Negative Microorganisms

Citrobacter (diversus) koseri

Enterobacter aerogenes

Escherichia coli

Haemophilus influenzae

Klebsiella pneumoniae

Neisseria gonorrhoeae

Proteus mirabilis

Pseudomonas aeruginosa

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with ofloxacin.

Other Microorganisms

Chlamydia trachomatis

The following in vitro data are available, but their clinical significance is unknown.

Ofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 mcg/mL or less against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of ofloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Aerobic Gram-Positive Microorganisms

Staphylococcus epidermidis (methicillin-susceptible strains)

Staphylococcus saprophyticus

Streptococcus pneumoniae (penicillin-resistant strains)

Aerobic Gram-Negative Microorganisms

Acinetobacter calcoaceticus

Bordetella pertussis

Citrobacter freundii

Enterobacter cloacae

Haemophilus ducreyi

Klebsiella oxytoca

Moraxella catarrhalis

Morganella morganii

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Serratia marcescens

Anaerobic Microorganisms

Clostridium perfringes

Other Microorganisms

Chlamydia pneumoniae

Gardnerella vaginalis

Legionella pneumophila

Mycoplasma hominis

Mycoplasma pneumoniae

Ureaplasma urealyticum

Ofloxacin is not active against Treponema pallidum (see WARNINGS).

Many strains of other streptococcal species, Enterococcus species, and anaerobes are resistant to ofloxacin.

Susceptibility Tests

Dilution Techniques:

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MIC values). These MIC values provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC values should be determined using a standardized procedure. Standardized procedures are based on a dilution method 1,3 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ofloxacin powder. The MIC values should be interpreted according to the following criteria:

For testing Enterobacteriaceae, methicillin-susceptible Staphylococcus aureus, and Pseudomonas aeruginosa:

For testing Haemophilus influenzae: a

a This interpretive standard is applicable only to broth microdilution susceptibility tests with Haemophilus influenzae using Haemophilus Test Medium. 1,3

The current absence of data on resistant strains precludes defining any results other than “Susceptible.” Strains yielding MIC results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.

For testing Neisseria gonorrhoeae: b

b These interpretive standards are applicable only to agar dilution tests using GC agar base and 1% defined growth supplement incubated in 5% CO 2.

For testing Streptococcus pneumoniae and Streptococcus pyogenes: c

c These interpretive standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard ofloxacin powder should provide the following MIC values:

d This quality control range is applicable only to H. influenzae ATCC 49247 tested by a microdilution procedure using Haemophilus Test Medium (HTM). 1,3

e This quality control range is applicable only to N. gonorrhoeae ATCC 49226 tested by an agar dilution procedure using GC agar base with 1% defined growth supplement incubated in 5% CO 2.

f This quality control range is applicable only to S. pneumoniae ATCC 49619 tested by a microdilution procedure using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood.

Diffusion Techniques:

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure 2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5 mcg ofloxacin to test the susceptibility of microorganisms to ofloxacin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5 mcg ofloxacin disk should be interpreted according to the following criteria:

For testing Enterobacteriaceae, methicillin-susceptible Staphylococcus aureus, and Pseudomonas aeruginosa:

For testing Haemophilus influenzae: g

g This zone diameter standard is applicable only to disk diffusion tests with Haemophilus influenzae using Haemophilus Test Medium (HTM) 2 incubated in 5% CO 2.

The current absence of data on resistant strains precludes defining any results other than “Susceptible.” Strains yielding zone diameter results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.

For testing Neisseria gonorrhoeae: h

h These zone diameter standards are applicable only to disk diffusion tests using GC agar base and 1% defined growth supplement incubated in 5% CO 2.

For testing Streptococcus pneumoniae and Streptococcus pyogenes: i

i These zone diameter standards are applicable only to disk diffusion tests performed using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood and incubated in 5% CO 2.

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for ofloxacin.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5 mcg ofloxacin disk should provide the following zone diameters in these laboratory quality control strains:

j This quality control range is applicable only to H. influenzae ATCC 49247 tested by a disk diffusion procedure using Haemophilus Test Medium (HTM) 2 incubated in 5% CO 2.

k This quality control range is applicable only to N. gonorrhoeae ATCC 49226 tested by a disk diffusion procedure using GC agar base with 1% defined growth supplement incubated in 5% CO 2.

l This quality control range is applicable only to S. pneumoniae ATCC 49619 tested by a disk diffusion procedure using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood and incubated in 5% CO 2.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ofloxacin tablets and other antibacterial drugs, ofloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Ofloxacin tablets are indicated for the treatment of adults with mild to moderate infections (unless otherwise indicated) caused by susceptible strains of the designated microorganisms in the infections listed below. Please see DOSAGE AND ADMINISTRATION for specific recommendations.

Acute Bacterial Exacerbations of Chronic Bronchitis (ABECB) due to Haemophilus influenzae or Streptococcus pneumoniae.

Because fluoroquinolones, including ofloxacin, have been associated with serious adverse reactions (see WARNINGS), and for some patients ABECB is self-limiting, reserve ofloxacin for treatment of ABECB in patients who have no alternative treatment options.

Community-Acquired Pneumonia due to Haemophilus influenzae or Streptococcus pneumoniae.

Uncomplicated Skin and Skin Structure Infections due to methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes, or Proteus mirabilis.

Acute, Uncomplicated Urethral and Cervical Gonorrhea due to Neisseria gonorrhoeae (see WARNINGS).

Nongonococcal Urethritis and Cervicitis due to Chlamydia trachomatis (see WARNINGS).

Mixed Infections of the Urethra and Cervix due to Chlamydia trachomatis and Neisseria gonorrhoeae (see WARNINGS).

Acute Pelvic Inflammatory Disease (including severe infection) due to Chlamydia trachomatis and/or Neisseria gonorrhoeae (see WARNINGS).

NOTE: If anaerobic microorganisms are suspected of contributing to the infection, appropriate therapy for anaerobic pathogens should be administered.

Uncomplicated Cystitis due to Citrobacter diversus, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa.

Because fluoroquinolones, including ofloxacin, have been associated with serious adverse reactions (see WARNINGS), and for some patients uncomplicated cystitis is self-limiting, reserve ofloxacin for treatment of uncomplicated cystitis in patients who have no alternative treatment options.

Complicated Urinary Tract Infections due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter diversus,* or Pseudomonas aeruginosa.*

Prostatitis due to Escherichia coli.

* = Although treatment of infections due to this organism in this organ system demonstrated a clinically significant outcome, efficacy was studied in fewer than 10 patients.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to ofloxacin, USP. Therapy with ofloxacin, USP may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with ofloxacin, USP. Culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agent but also on the possible emergence of bacterial resistance.

Ofloxacin tablets are contraindicated in persons with a history of hypersensitivity associated with the use of ofloxacin or any member of the quinolone group of antimicrobial agents.

The following is a compilation of the data for ofloxacin based on clinical experience with both the oral and intravenous formulations. The incidence of drug-related adverse reactions in patients during Phase 2 and 3 clinical trials was 11%. Among patients receiving multiple-dose therapy, 4% discontinued ofloxacin due to adverse experiences.

In clinical trials, the following events were considered likely to be drug-related in patients receiving multiple doses of ofloxacin:

nausea 3%, insomnia 3%, headache 1%, dizziness 1%, diarrhea 1%, vomiting 1%, rash 1%, pruritus 1%, external genital pruritus in women 1%, vaginitis 1%, dysgeusia 1%.

In clinical trials, the most frequently reported adverse events, regardless of relationship to drug, were:

nausea 10%, headache 9%, insomnia 7%, external genital pruritus in women 6%, dizziness 5%, vaginitis 5%, diarrhea 4%, vomiting 4%.

In clinical trials, the following events, regardless of relationship to drug, occurred in 1 to 3% of patients:

abdominal pain and cramps, chest pain, decreased appetite, dry mouth, dysgeusia, fatigue, flatulence, gastrointestinal distress, nervousness, pharyngitis, pruritus, fever, rash, sleep disorders, somnolence, trunk pain, vaginal discharge, visual disturbances, and constipation.

Additional events, occurring in clinical trials at a rate of less than 1%, regardless of relationship to drug, were:

The following laboratory abnormalities appeared in ≥ 1.0% of patients receiving multiple doses of ofloxacin. It is not known whether these abnormalities were caused by the drug or the underlying conditions being treated.

Postmarketing Adverse Events

Additional adverse events, regardless of relationship to drug, reported from worldwide marketing experience with quinolones, including ofloxacin:

Clinical

Laboratory

In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with other quinolones. The relationship of the drugs to these events is not presently established.

CRYSTALLURIA and CYLINDRURIA HAVE BEEN REPORTED with other quinolones.

Information on overdosage with ofloxacin is limited. One incident of accidental overdosage has been reported. In this case, an adult female received 3 grams of ofloxacin intravenously over 45 minutes. A blood sample obtained 15 minutes after the completion of the infusion revealed an ofloxacin level of 39.3 mcg/mL. In 7 h, the level had fallen to 16.2 mcg/mL, and by 24 h to 2.7 mcg/mL. During the infusion, the patient developed drowsiness, nausea, dizziness, hot and cold flushes, subjective facial swelling and numbness, slurring of speech, and mild to moderate disorientation. All complaints except the dizziness subsided within 1 h after discontinuation of the infusion. The dizziness, most bothersome while standing, resolved in approximately 9 h. Laboratory testing reportedly revealed no clinically significant changes in routine parameters in this patient.

In the event of an acute overdose, the stomach should be emptied. The patient should be observed and appropriate hydration maintained. Ofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis.

The usual dose of Ofloxacin Tablets, USP is 200 mg to 400 mg orally every 12 h as described in the following dosing chart. These recommendations apply to patients with normal renal function (i.e., creatinine clearance > 50 mL/min). For patients with altered renal function (i.e., creatinine clearance ≤ 50 mL/min), see the Patients with Impaired Renal Function subsection.

Antacids containing calcium, magnesium, or aluminum; sucralfate; divalent or trivalent cations such as iron; or multivitamins containing zinc; or didanosine, chewable/buffered tablets or the pediatric powder for oral solution should not be taken within the two-hour period before or within the two-hour period after taking ofloxacin (see PRECAUTIONS).

Patients with Impaired Renal Function

Dosage should be adjusted for patients with a creatinine clearance ≤ 50 mL/min. After a normal initial dose, dosage should be adjusted as follows:

When only the serum creatinine is known, the following formula may be used to estimate creatinine clearance.

Women: 0.85 × the value calculated for men.

The serum creatinine should represent a steady-state of renal function.

Patients with Cirrhosis

The excretion of ofloxacin may be reduced in patients with severe liver function disorders (e.g., cirrhosis with or without ascites). A maximum dose of 400 mg of ofloxacin per day should therefore not be exceeded.

Ofloxacin Tablets, USP 400 mg are white, modified capsule shaped, biconvex film coated tablets. Each tablet is distinguished by an imprint of “LL713” on one side and blank on the other side. They are available in bottles of 100 tablets (NDC 68047-713-01) and 20 tablets (NDC 68047-713-20).

Ofloxacin Tablets, USP should be stored in well-closed containers. Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Ofloxacin, as well as other drugs of the quinolone class, has been shown to cause arthropathies (arthrosis) in immature dogs and rats. In addition, these drugs are associated with an increased incidence of osteochondrosis in rats as compared to the incidence observed in vehicle-treated rats (see WARNINGS). There is no evidence of arthropathies in fully mature dogs at intravenous doses up to 3 times the recommended maximum human dose (on a mg/m 2 basis or 5 times based on mg/kg basis), for a one-week exposure period.

Long-term, high-dose systemic use of other quinolones in experimental animals has caused lenticular opacities; however, this finding was not observed in any animal studies with ofloxacin.

Reduced serum globulin and protein levels were observed in animals treated with other quinolones. In one ofloxacin study, minor decreases in serum globulin and protein levels were noted in female cynomolgus monkeys dosed orally with 40 mg/kg ofloxacin daily for one year. These changes, however, were considered to be within normal limits for monkeys.

Crystalluria and ocular toxicity were not observed in any animals treated with ofloxacin.

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Eleventh Edition. CLSI document M02-A11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-third Informational Supplement, CLSI document M100-S24, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2014.

Manufactured for:

Larken Laboratories, Inc.

Canton, Mississippi 39046

Toll Free: 1-601-855-7678

Rx Only

Rev. 08/20

OFLOXACIN TABLETS (oh floks' a sin)

Rx only

Read the Medication Guide that comes with ofloxacin before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about ofloxacin tablets?

Ofloxacin belongs to a class of antibiotics called fluoroquinolones. Ofloxacin tablets can cause serious side effects. Some of these serious side effects can happen at the same time and could result in death. If you get any of the following serious side effects, get medical help right away. Talk with your healthcare provider about whether you should continue to take ofloxacin tablets.

1. Tendon rupture or swelling of the tendon (tendinitis)

• Tendon problems can happen in people of all ages who take ofloxacin tablets. Tendons are tough cords of tissue that connect muscles to bones.
  • Pain, swelling, tears, and inflammation of tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.
• The risk of getting tendon problems while you take ofloxacin tablets is higher if you:
  • are over 60 years of age
  • are taking steroids (corticosteroids)
  • have had a kidney, heart or lung transplant.
• Tendon problems can happen in people who do not have the above risk factors when they take ofloxacin tablets. Other reasons that can increase your risk of tendon problems can include:
  • physical activity or exercise
  • kidney failure
  • tendon problems in the past, such as in people with rheumatoid arthritis (RA).
• Stop taking ofloxacin immediately and get medical help right away at the first sign of tendon pain, swelling or inflammation. Stop taking ofloxacin tablets until tendinitis or tendon rupture has been ruled out by your healthcare provider. Avoid exercise and using the affected area. The most common area of pain and swelling is the Achilles tendon at the back of your ankle. This can also happen with other tendons.
• Talk to your healthcare provider about the risk of tendon rupture with continued use of ofloxacin tablets. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.
• Tendon rupture can happen while you are taking or after you have finished taking ofloxacin tablets. Tendon ruptures have happened up to several months after patients have finished taking their fluoroquinolone.
• Get medical help right away if you get any of the following signs or symptoms of a tendon rupture:
  • hear or feel a snap or pop in a tendon area
  • bruising right after an injury in a tendon area
  • unable to move the affected area or bear weight

2. Changes in sensation and possible nerve damage (Peripheral Neuropathy). Damage to the nerves in arms, hands, legs, or feet can happen in people who take fluoroquinolones, including ofloxacin. Stop taking ofloxacin immediately and talk to your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:

• pain
• burning
• tingling
• numbness
• weakness

The nerve damage may be permanent.

3. Central Nervous System (CNS) effects. Seizures have been reported in people who take fluoroquinolone antibacterial medicines, including ofloxacin. Tell your healthcare provider if you have a history of seizures before you start taking ofloxacin. CNS side effects may happen as soon as after taking the first dose of ofloxacin. Stop taking ofloxacin immediately and talk to your healthcare provider right away if you get any of these side effects, or other changes in mood or behavior:

• seizures
• hear voices, see things, or sense things that are not there (hallucinations)
• feel restless
• tremors
• feel anxious or nervous
• confusion
• depression
• trouble sleeping
• nightmares
• feel lightheaded or dizzy
• feel more suspicious (paranoia)
• suicidal thoughts or acts
• headaches that will not go away, with or without blurred vision

4. Worsening of myasthenia gravis (a disease that causes muscle weakness).

Fluoroquinolones like ofloxacin tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.

See the section "What are the possible side effects of ofloxacin tablets?" for more information about side effects.

What is ofloxacin?

Ofloxacin tablets are a fluoroquinolone antibiotic medicine used in adults to treat certain infections caused by certain germs called bacteria. It is not known if ofloxacin tablets are safe and work in people under 18 years of age. Children less than 18 years of age have a higher chance of getting bone, joint, or tendon (musculoskeletal) problems such as pain or swelling while taking ofloxacin tablets.

Sometimes infections are caused by viruses rather than by bacteria. Examples include viral infections in the sinuses and lungs, such as the common cold or flu. Antibiotics, including ofloxacin tablets, do not kill viruses.

Call your healthcare provider if you think your condition is not getting better while you are taking ofloxacin tablets.

Who should not take ofloxacin tablets?

Do not take ofloxacin tablets if you have ever had a severe allergic reaction to an antibiotic known as a fluoroquinolone, or if you are allergic to any of the ingredients in ofloxacin. Ask your healthcare provider if you are not sure. See the list of the ingredients in ofloxacin tablets at the end of this Medication Guide.

What should I tell my healthcare provider before taking ofloxacin tablets?

See "What is the most important information I should know about ofloxacin tablets?"

Tell your healthcare provider about all your medical conditions, including if you:

• have tendon problems- ofloxacin should not be used in patients who have a history of tendon problems
• have a disease that causes muscle weakness (myasthenia gravis)
• have central nervous system problems (such as epilepsy)
• have nerve problems- ofloxacin should not be used in patients who have a history of nerve problems called peripheral neuropathy
• have or anyone in your family has an irregular heartbeat, especially a condition called "QT prolongation."
• have low blood potassium (hypokalemia)
• have a history of seizures
• have kidney problems. You may need a lower dose of ofloxacin tablets if your kidneys do not work well.
• have liver problems
• have rheumatoid arthritis (RA) or other history of joint problems
• are pregnant or planning to become pregnant. It is not known if ofloxacin tablets will harm your unborn child.
• are breastfeeding or planning to breastfeed. Ofloxacin passes into breast milk. You and your healthcare provider should decide whether you will take ofloxacin tablets or breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, herbal and dietary supplements. Ofloxacin tablets and other medicines can affect each other causing side effects. Especially tell your healthcare provider if you take:

• an NSAID (Non-Steroidal Anti-Inflammatory Drug). Many common medicines for pain relief are NSAIDs. Taking an NSAID while you take ofloxacin tablets or other fluoroquinolones may increase your risk of central nervous system effects and seizures. See " What are the possible side effects of ofloxacin tablets?"
• theophylline
• a blood thinner (warfarin, Coumadin ®, Jantoven ®)
• an oral anti-diabetes medicine or insulin
• a medicine to control your heart rate or rhythm (antiarrhythmics). See "What are the possible side effects of ofloxacin tablets?".
• an anti-psychotic medicine
• a tricyclic antidepressant
• a water pill (diuretic)
• a steroid medicine. Corticosteroids taken by mouth or by injection may increase the chance of tendon injury. See "What is the most important information I should know about ofloxacin tablets?".
• Certain medicines may keep ofloxacin tablets from working correctly. Take ofloxacin tablets either 2 hours before or 2 hours after taking these products:
  • an antacid, multivitamin, or other product that has magnesium, aluminum, iron, or zinc.
  • sucralfate (Carafate ®)
  • didanosine (Videx ®,Videx ® EC)

Ask your healthcare provider if you are not sure if any of your medicines are listed above. Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take ofloxacin tablets?

• Take ofloxacin tablets exactly as prescribed by your healthcare provider.
• Take ofloxacin tablets at about the same time each day.
• Drink plenty of fluids while taking ofloxacin tablets.
• Ofloxacin tablets can be taken with or without food.
• Do not skip any doses, or stop taking ofloxacin tablets even if you begin to feel better, until you finish your prescribed treatment, unless:
  • you have tendon effects (see "What is the most important information I should know about ofloxacin tablets?")
  • you have nerve problems (see “What is the most important information I should know about ofloxacin tablets?”)
  • you have central nervous system problems (see “What is the most important information I should know about ofloxacin tablets?”)
  • you have a serious allergic reaction (see "What are the possible side effects of ofloxacin tablets?”), or
  • your healthcare provider tells you to stop.
• This will help make sure that all of the bacteria are killed and lower the chance that the bacteria will become resistant to ofloxacin tablets. If this happens, ofloxacin tablets and other antibiotic medicines may not work in the future.
• If you miss a dose of ofloxacin tablets, take it as soon as you remember. Do not take two doses of ofloxacin tablets at the same time. Do not take more than two doses in one day.
• If you take too much, call your healthcare provider or get medical help immediately.

What should I avoid while taking ofloxacin tablets?

• Ofloxacin tablets can make you feel dizzy and lightheaded. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how ofloxacin tablets affect you.
• Avoid sunlamps, tanning beds, and try to limit your time in the sun. Ofloxacin tablets can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while taking ofloxacin tablets, call your healthcare provider right away. You should use a sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight.

What are the possible side effects of ofloxacin tablets?

Changes in blood sugar

People who take fluoroquinolone medicines with oral anti-diabetes medicines or with insulin can get low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia). Follow your healthcare provider's instructions for how often to check your blood sugar. If you have diabetes and you get low blood sugar while taking ofloxacin, stop taking ofloxacin and call your healthcare provider right away. Your antibiotic medicine may need to be changed.

Ofloxacin tablets can cause side effects that may be serious or even cause death. See "What is the most important information I should know about ofloxacin tablets?"

Other serious side effects of ofloxacin tablets include:

• Serious allergic reactions.

  Allergic reactions can happen in people taking fluoroquinolones, including ofloxacin tablets, even after only one dose. Stop taking ofloxacin tablets and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:

  • hives
  • trouble breathing or swallowing
  • swelling of the lips, tongue, face
  • throat tightness, hoarseness
  • rapid heartbeat
  • faint

• Yellowing of the skin or eyes
  
  Stop taking ofloxacin tablets and tell your healthcare provider right away if you get yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to ofloxacin tablets (a liver problem).
• Aortic aneurysm and dissection
  
  Tell your healthcare provider if you have ever been told that you have an aortic aneurysm, a swelling of the large artery that carries blood from the heart to the body. Get emergency medical help right away if you have sudden chest, stomach, or back pain. Get emergency medical help right away if you have sudden chest, stomach, or back pain.
• Skin rash
  
  Skin rash may happen in people taking ofloxacin tablets, even after only one dose. Stop taking ofloxacin tablets at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to ofloxacin.
• Intestine infection (Pseudomembranous colitis)
  
  Pseudomembranous colitis can happen with most antibiotics, including ofloxacin tablets. Call your healthcare provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you have finished your antibiotic.
• Serious heart rhythm changes (QT prolongation and torsade de pointes)
  
  Tell your healthcare provider right away if you have a change in your heart beat (a fast or irregular heartbeat), or if you faint. Ofloxacin tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this happening are higher in people:
  • who are elderly
  • with a family history of prolonged QT interval
  • with low blood potassium (hypokalemia)
  • who take certain medicines to control heart rhythm (antiarrhythmics)

• Sensitivity to sunlight (photosensitivity): See " What should I avoid while taking ofloxacin tablets?"
• Low blood sugar (hypoglycemia). People who take ofloxacin tablets and other fluoroquinolone medicines with oral anti-diabetes medicines or with insulin can get low blood sugar (hypoglycemia). Follow your healthcare provider's instructions for how often to check your blood sugar. If you have diabetes and you get low blood sugar while taking ofloxacin tablets, stop taking ofloxacin tablets right away and call your healthcare provider right away. Your antibiotic medicine may need to be changed.

The most common side effects of ofloxacin tablets include:

• Sleep problems
• headache
• dizziness
• nausea
• vomiting
• diarrhea
• itching
• external genital itching in women
• vaginal inflammation (vaginitis)
• taste changes

Ofloxacin tablets may cause false-positive urine screening results for opiates when testing is done with some commercially available kits. A positive result should be confirmed using a more specific test.

These are not all the possible side effects of ofloxacin tablets. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store ofloxacin tablets?

• Store ofloxacin tablets at 20° to 25°C (68° to 77°F).
• Keep the bottle that ofloxacin tablets come in closed tightly.
• Keep ofloxacin tablets and all medicines out of the reach of children.

General Information about ofloxacin tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ofloxacin tablets for a condition for which it is not prescribed. Do not give ofloxacin tablets to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about ofloxacin tablets. If you would like more information about ofloxacin tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ofloxacin tablets that is written for healthcare professionals. For more information call 1-601-855-7678 or go to www.larkenlabs.com.

What are the ingredients in ofloxacin tablets?

Active ingredient: ofloxacin, USP

Inactive ingredients: anhydrous lactose, modified corn starch, hydroxypropyl cellulose, hypromellose, magnesium stearate, polyethylene glycol, polysorbate 80, sodium starch glycolate, and titanium dioxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Larken Laboratories, Inc.

Canton, Mississippi 39046

Rev. 05/19

20 ct. bottle label for Ofloxacin Tablets, USP 400 mg